JMIR Publications

ABSTRACT

Background:

Iron deficiency is the most widespread nutritional deficiency globally and the primary cause of anemia, particularly in low and middle-income countries such as Indonesia. Iron deficiency has a multifactorial etiology involving complex interactions between genetic factors, especially the transmembrane protease serine 6 (TMPRSS6) rs855791 gene, which encodes matriptase-2, a protein involved in regulating hepcidin expression, and nongenetic factors including socio-demographics, nutritional status, iron intake, and menstrual patterns. Females of reproductive age, including medical students are vulnerable to iron deficiency owing to, unhealthy dietary habits, growth and menstruation. The impact of iron deficiency on medical students can cause decreased academic performance and productivity. Additionally, as future mothers, they experience a heightened risk of delivering children with intellectual disorders and various psychosocial impairments. Owing to the significant consequences of its impact, identifying the underlying causes of condition is crucial. The high prevalence of iron deficiency in Indonesia poses a challenge in addressing these contributing factors effectively reduce its occurrence.

Objective:

This study aims to investigate the association of the-TMPRSS6 rs855791 variant and nongenetic factors with iron deficiency among female medical students in Yogyakarta, Indonesia.

Methods:

This is a case - control study. Participants will be recruited from female students at the Faculty of Medicine, Public Health, and Nursing Universitas Gadjah Mada in Yogyakarta, Indonesia. The inclusion criteria will encompass female medical students, aged 18 - 24 years, not pregnant, with written consent, no history of chronic and inflammatory diseases, congenital diseases, hematological disorders, and blood transfusion during the last 3 months. Participants will be excluded when the C-Reactive Protein level is > 5 mg/dL. Participants will be further grouped according to the iron status criteria. Profiles of hemogram and iron markers will be compared between the case and control groups using the unpaired T-test or the Mann-Whitney U test, while genotype and allele frequencies will be analyzed using the chi-squared test. The ANOVA test will be used to assess the impact of different genotyping variants on iron marker levels. Multivariate analysis will be performed with the logistic regression test to determine factors independently associated with iron deficiency risk. P-values ≤ 0.05 will be considered statistically significant.

Results:

The ethical approval for this study has gained permission from the Medical and Health Research Ethics Committee of the Faculty of Medicine, Public Health and Nursing, Universitas Gajah Mada (FMPHN UGM) in Yogyakarta, Indonesia (approval number: KE/FK/0114/EC/2025; January 24, 2025). Data collection commenced in February 2025, and the findings are expected to be published in 2026

Conclusions:

This study will determine the interaction between the TMPRSS6 rs855791 variant and nongenetic factors that contribute to the risk of iron deficiency among female medical students in Yogyakarta, Indonesia.